We will critically test the hypothesis of selective neutrality of naturally occurring electrophoretic enzyme variants using Escherichia coli in chemostats. Initially we will study the full range of naturally occurring allelic variation at two loci, and (6-phosphogluconate dehydrogenase) and mdh (malate dehydrogenase); other loci will be studied subsequently. By studying competition between isogenic strains in chemostats, we will empirically define physiologically stressful environments for each locus as those in which selection between plus and minus strains is maximal (minus strains will be mutants having no active enzyme); similarly, physiologically nonstressful environments will be empirically defined as those in which selection between plus and minus strains is minimal. Pairs of electrophoretic variants made effectively isogenic by transduction will then be competed in chemostats in both stress and nonstress environments, and the selection coefficients will be estimated. The finding of no selection, or drastically reduced selection, in the nonstress environment serves to control against the possibility that the selection is due to loci closely linked to the tested locus. With this system, accurate estimates of selection coefficients as small as 0.01 percent can be achieved, in replicate. The empirical distribution of selection coefficients of naturally occurring variants will then be compared with the distribution of selection coefficients of new (created in the laboratory and unselected) electrophoretically detectable variants. Homogenotes and heterogenotes for the loci under study will also be examined as a test of the hypothesis of molecular heterosis.